Hemoglobin-based oxygen carriers (HBOCs) were initially developed as blood substitutes. Human placenta hemoglobin is a particularly promising HBOC. It allows transporting more oxygen to hypoxic tissues owing to its higher oxygen affinity, lower viscosity, and smaller mean diameter than human red blood cells. However, the major problems posed by the use of placenta hemoglobin on a large scale are caused by the conditions under which it is extracted from the placentas and purified. Placentas are kept in frozen storage and to extract hemoglobin they have to be crushed before thawing. Then, tissues and fibrinogen are removed by filtration and several steps of chromatography, precipitation and diafiltration are carried out on the resulting filtrate. Also, the sources of human placenta hemoglobin and human blood are limited. Therefore, the construction and expression of recombinant hemoglobin protein or recombinant hemoglobin tetramer or dimer or subunits are important to solve this issue.
Hypoxia is common in cancers. Hypoxia and anemia (which contributes to tumor hypoxia) can lead to ionizing radiation and chemotherapy resistance by depriving tumor cells of the oxygen essential for the cytotoxic activities of these agents. Hypoxia may also reduce tumor sensitivity to radiation therapy and chemotherapy through one or more indirect mechanisms that include proteomic and genomic changes. Therefore, there is a need for improved cancer-treatment compositions, particularly, improved cancer-treatment compositions that facilitate targeting cancer cells and enhance the efficacy of cytotoxic agents.